Nitric Oxide (NO) is a ubiquitous small molecule messenger involved in many pathological and physiological processes. NO plays critical roles in vascular and neuronal signal transduction pathways, smooth muscle contractility, bioenergetics, platelet adhesion and aggregation, immunity, and cell death regulation. NO deficiency is implicated in many pathophysiological processes such as hypertension, cardiovascular dysfunctions, neurodegeneration, arthritis, asthma and septic shock. NO is one of the few gaseous signaling molecules known and is additionally exceptional due to the fact that it is a radical gas. It is a known byproduct in almost all types of organisms, ranging from bacteria to plants, fungi, and animal cells.
There are several mechanisms by which NO has been demonstrated to affect the biology of living cells. These include oxidation of iron-containing proteins such as ribonucleotide reductase and aconitase, activation of the soluble guanylate cyclase, ADP ribosylation of proteins, protein sulfhydryl group nitrosylation, and iron regulatory factor activation. NO has also been demonstrated to activate NF-κB in peripheral blood mononuclear cells, an important transcription factor in iNOS gene expression in response to inflammation. Additionally, during an immune response, NO is secreted as free radicals and is toxic to many bacteria and intracellular parasites; NO causes DNA damage and degradation of iron sulfur centers into iron ions and iron-nitrosyl compounds.
The administration of exogenous NO not only constitutes a powerful way to supplement NO when a subject cannot generate enough for normal biological functions, it also offers a means for accelerating wound healing and reducing bioburden in a subject. NO produced by both iNOS and eNOS plays many important roles in wound healing, from the inflammatory phase through to scar remodeling. In particular, NO exerts cytostatic, chemotactic, and vasodilatory effects during early wound repair, regulates proliferation and differentiation of several cell types, modulates collagen deposition and angiogenesis, and affects wound contraction. However, the timing, concentration, pressurization, and site of NO administration are all poorly understood critical factors affecting the ability of NO to facilitate wound repair.